Serotype of Streptococcus pneumoniae capsular polysaccharide can modify the Th1/Th2 cytokine profile and IgG subclass response to pneumococal-CRM197 conjugate vaccines in a murine model

The cellular and antibody responses to type 14 and type 19F Streptococcus p neumoniae capsular polysaccharides (PS) conjugated to CRM197 were investiga ted in a mouse model developed for pre-clinical evaluation and quality cont rol of pneumococcal conjugate vaccines. Total IgG antibody and IgG subclass es against PS and the carrier protein for both conjugates were measured in addition to the T cell proliferation and cytokine profiles induced by these conjugates. While unconjugated PS 14 and 19F were at best only weakly immu nogenic, both types of conjugate induced strong primary and secondary IgG r esponses to PS. The responses induced by the two conjugates to the carrier protein were very different; a high level of anti-CRM197 IgG was induced on ly by the PS19F conjugate whereas a very weak response was induced by the P S14 conjugate. Interestingly, the Ige subclass distribution was different f or the two conjugates; for PS19F conjugate, the Ige response was almost com pletely of IgG1 subclass with low levels of IgG3 and IgG2a while the respon se to PS14 conjugate was mainly of the IgG1 and IgG2a subclasses with a low level of IgG3. The anti-CRM197 IgG subclass distribution was identical wit h that to the corresponding conjugated PS. Both types of conjugate induced strong T cell proliferation to recall antigens but induced different patter ns of cytokine response in immune spleen cells which were indicative of a T h0 response or a mixture of Th1 and Th2 responses with a bias towards Th2 r esponse in PS19F-CRM197 immunised mice. In conclusion, PS14- and PS19F-CRM1 97 conjugates induced different IgG subclass patterns as a result of induci ng different patterns of cytokine response to the carrier protein. This ind icates that the serotype of PS can modify the Th1/Th2 response to the carri er protein, which has a direct effect and can predict the IgG subclass of t he PS response. Finally, we conclude that this model appears suitable for s tudying the immunogenicity and immune interaction of different components o f multivalent pneumococcal conjugate vaccines and may be applicable to thei r pre-clinical evaluation and quality control. (C) 2000 Elsevier Science Lt d. All rights reserved.